Genetic mutations (natural or induced) in humans and animals have revealed roles of particular ion channels in normal physiology and diseases such as pain, epilepsy and paralysis. An autosomal dominant mutant mouse generated by ENU mutagenesis becomes apparently temporarily paralyzed upon handling (Possum), and this phenotype is due to a point mutation in a single ion channel gene predominantly expressed in nociceptors. Since Possum mice may be a useful animal model for pathophysiologies caused by nociceptor hyperactivity, I propose to characterize the voltage and kinetic properties of the mutant channel at a biophysical level, the excitability of nociceptors expressing the mutant channel, and behavioral responses to various stimuli. PUBLIC HEALTH RELEVANCE: Pathophysiological behavioral phenotypes produced by mutations in a single ion channel gene provide a unique opportunity to discover the effects of aberrant channel activity on cellular function and system dynamics. A point mutation in a nociceptive ion channel produces a novel temporary paralysis phenotype when the mice are handled. We will determine the effect of the mutation on channel function, and native sensory neuron excitability and sensitivity noxious stimuli.